This invention relates to amino acid chelated mineral compositions containing amino acid ligands which have improved palatability. More particularly, this invention relates to amino acid chelated mineral compositions wherein the coordination number of the metal is satisfied by an organic electron donor moiety and wherein the ligands are charge balanced to neutralize electron donor or Lewis Base sites resulting in amino acid chelates which are essentially free of objectional taste.
In the formation of metal complexes and/or chelates there are actually two valencies or binding sites for the central metal ion which should be considered. The first is the "primary valence" (oxidation state) exhibited by the metal ion, e.g. copper as copper(I) or cuprous (+1) and copper(II) or cupric (+2) ions; iron as iron(II) or ferrous (+2) and iron(III) or ferric (+3) ions, zinc as zinc(II) or zinc (+2) ions; calcium as calcium(II) or calcium (+2) ions; manganese as manganese(II) or manganese (+2) and manganese(III) or manganese (+3) ions; magnesium as magnesium(II) or magnesium (+2) ions; chromium as chromium(II) or chromium (+2) and chromium(III) or chromium (+3) ions and cobalt as cobalt(II) or cobalt (+2) and cobalt(III) or cobalt (+3) ions. Additonally, there is a secondary valency of a central metal ion directed to specific position in the coordination sphere which is the total number of bonds the metal forms with ligands, i.e. a molecule containing a functional grouping which can serve as an electron donor and form a coordinating bond. Ligands can vary from molecules as simple as water or ammonia to complex polydentate ligands having two or more electron donor sites capable of chelate formation.
The secondary valence of the central metal ion is referred to as the "coordination number". Numbers ranging from 2 to 12 have been observed but numbers of 2, 4 and 6, and sometimes 8, are the most common. Of the metals of interest in the present invention, coordination numbers of 2 and 4 are found mostly in Cu(I) with 2 being the most common. Copper(II) has coordination numbers of 4 or 6. Iron(II) has a coordination number of 6 and Iron(III) has coordination numbers of 4 or 6. Zinc(II) has coordination numbers of 4 or 6. Calcium has coordination numbers of 6 and 8. Magnesium(II), manganese(II) and manganese(III) each have a coordination number of 6. Additionally, cobalt(II), cobalt(III), chromium(II) and chromium(III) each have a coordination number of 6.
The coordination number assigned to a central metal ion depends on a number of variables or factors. Representative of these are the ratio of the radius of the central metal ion to that of the attached ligands. As the ligand gets larger fewer ligands can coordinate with the metal. Also, ligands that transfer a negative charge to the metal also result in reduced coordination numbers.
When a metal combines with an electron donor ligand, a complex or coordination compound is formed. When the electron donor contains two or more donor groups tied together in some way, the ligand is referred to as a polydentate ligand, e.g. a bidentate ligand has two donor groups, and the resulting complex is a chelate. The essential and characteristic feature found in all chelates is formation of a ring of bonded atoms between the ligand and the metal atom. For ring formation to occur, the electron donor molecule must contain two or more groups that can each combine with the metal atom. Groups or atoms (e.g. oxygen, nitrogen, hydroxyl, and amino) must be present that can coordinate with the metal atom through their electron pairs. These donor groups must be separated from each other by chains of suitable length to form sterically permissible rings.
.alpha.-Amino acids comprise a group of ligands that have been used to chelate minerals. It is known that .alpha.-amino acid chelates form a stable product having one or more five-member rings formed by reactions between the carboxyl oxygen and the .alpha.-amino group of an .alpha.-amino acid with the metal ion. Such a five-member ring is defined by the metal atom, the carboxyl oxygen, the carbonyl carbon, the a-carbon, and the .alpha.-amino nitrogen and is generally represented by the Formula I. However, the actual structure will depend upon the ligand to metal mole ratio and whether monosubstituting unidentate ligands are also utilized. The ligand to metal ratio is at least 1:1 and is preferably 2:1, but in certain instances may be 3:1 or even 4:1 with bidentate ligands, depending upon the coordination numbers of the metal ion and the size and steric configuration of the ligands. If monodentate ligands are used in conjunction with a single bidentate ligand, such as an .alpha.-amino acid, then ratios could be up to 7:1 for calcium with a coordination number of eight. Most typically, an amino acid chelate may be represented at a ligand to metal ratio of 2:1 according to the following formula: ##STR1##
In the above formula M is a member selected from the group consisting of copper, iron, manganese, zinc, magnesium, calcium, cobalt and chromium. The R moieties can be the same or different, i.e. can represent dissimilar amino acid ligands making up the chelate. When R is H, the amino acid is glycine, the simplest of the .alpha.-amino acids. However, R could represent any of the side chains of the other twenty or so naturally occurring .alpha.-amino acids derived from proteins or additionally additional metabolic .alpha.-amino acids any synthetically produced .alpha.-amino acid. R' is a member selected from the group consisting of H or [--C(O)CHRNH.sub.2 --].sub.e H wherein R is as defined above and e is an integer of 1 or 2. When e is 1 or 2 the ligand becomes a di- or tripeptide of amino acids (i.e. hydrolyzed protein fragments) or any synthetically produced .alpha.-amino acid or amino acid chains. These .alpha.-amino acids all have the same configuration for the positioning of the carboxyl oxygen and the .alpha.-amino nitrogen. In other words, the chelate ring is defined by the same atoms in each instance. The American Association of Feed Control Officials (AAFCO) has also issued a definition for an amino acid chelate. It is officially defined as the product resulting from the reaction of a metal ion from a soluble metal salt with amino acids with a mole ratio of one mole of metal to one to three (preferably two) moles of amino acids to form coordinate covalent bonds. The average weight of the hydrolyzed amino acids must be approximately 150 and the resulting molecular weight of the chelate must not exceed 800. The products are identified by the metal forming the chelate, i.e. iron amino acid chelate, copper amino acid chelate, etc.
According to the above, amino acid chelates can also be formed using dipeptide or tripeptide ligands. A representative tripeptide is shown in Formula II: ##STR2## where R is as defined above. The R groups are independent of each other and can represent a tripeptide of the same or different amino acids. Ligands larger than tripeptides possess at least two drawbacks. First, sterically, they may be too large in size to conveniently form a chelate wherein all of the coordination sites are occupied by an electron donor. Secondly, they would have a molecular weight which would be too great for direct intestinal absorption of the chelate formed. Generally, peptide ligands will be derived by the hydrolysis of protein. However, peptides prepared by conventional synthetic techniques or genetic engineering can also be used. When a ligand is a di- or tripeptide, R, as defined in Formula I, can be H, or the side chain of any other naturally occurring or synthetically prepared amino acid and e can be an integer of 1 or 2. When e is 1 the ligand will be a dipeptide and when e is 2 the ligand will be a tripeptide, but the moieties of chelation will derive from the carboxyl end of the dipeptide or tripeptide chain, rather than the amino terminis. The carboxyl oxygen and nearby a-nitrogen of the same terminal amino acide will be the chelating portions of the dipeptide or tripeptide chain. As noted above, the R moieties are independent in that different R groups can be contained on ligands forming the chelate and, in the case of di- or tripeptides, different amino acids can make up the peptide chain.
The structure, chemistry, and bioavailability of amino acid chelates is well documented in the literature, e.g. Ashmead et al., Chelated Mineral Nutrition in Plants, Animals and Man, (1982), Chas. C. Thomas Publishers, Springfield, Ill.; Ashmead et al., Intestinal Absorption of Metal Ions and Chelates, (1985), Chas. C. Thomas Publishers, Springfield, Ill.; Ashmead et al., Foliar Feeding of Plants with Amino Acid Chelates, (1986), Noyes Publications, Park Ridge, N.J.; The Roles of Amino Acid Chelates in Animal Nutrition, (1993), Noyes Publications, Park Ridge, N.J.; as well as in U.S. Pat. Nos. 4,020,158; 4,167,564; 4,216,143; 4,216,144; 4,599,152; 4,774,089; 4,830,716; 4,863,898 and others. Flavored effervescent mixtures of vitamins and amino acid chelates for administration to humans in the form of a beverage are disclosed in U.S. Pat. No. 4,725,427.
In the field of mineral nutrition, amino acid chelates have increasingly been recognized as providing certain advantages over inorganic mineral salts. One advantage is attributed to the fact that these chelates are readily absorbed in the gut and mucosal cells by means of active transport as though they were amino acids or small peptides. In other words, the minerals are absorbed along with the amino acids as a single unit utilizing the amino acids as carrier molecules. Since this method of absorption does not involve the absorption sites for free metal ions, the problems of competition of ions for active sites and suppression of one nutritive mineral element by another are avoided. Other advantages of amino acid chelates include stimulation of gonadotropic hormones, U.S. Pat. No. 4,774,089; delivery of metal ions to targeted tissue sites, U.S. Pat. No. 4,863,898; and enhancement of the immune system, U.S. Pat. No. 5,162,369.
Despite these advantages, use of amino acid chelates for human and animal consumption has the drawback of a metallic flavor or aftertaste that some people and animals find unpleasant or disagreeable. Thus, amino acid chelates have had to be taken in capsules and other forms that avoid this aftertaste. Use of amino acid chelates in nutritional beverages has also been limited by this disagreeable flavor. It was commonly believed that the metallic aftertaste of mineral amino acid chelates was due to the metal portion of the chelates. However, it has now been found that the aftertaste of the chelates may be due to a variety of factors associated with incomplete filling of all coordination binding sites of the metal ion and the charge associated with the ligand following the chelation of the ligand(s) to the metal ion.
In view of the foregoing, it will be appreciated that amino acid chelates having improved palatability would be a significant advancement in the art.